Evaluating the Efficacy and Safety of the Lower Dose of Bortezomib Plus Busulfan and Melphalan as a Conditioning Regimen in Patients With Multiple Myeloma Undergoing Autologous Peripheral Blood Stem Cell Transplantation- KMM103 Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Yonsei University
Sponsor:
Information provided by (Responsible Party):
Yonsei University
ClinicalTrials.gov Identifier:
NCT01255527
First received: December 6, 2010
Last updated: June 1, 2013
Last verified: June 2013
  Purpose

Despite the advantages of autologous stem cell transplantation (ASCT) over conventional chemotherapy,1,2 the results of high-dose chemoradiotherapy in multiple myeloma (MM) are still unsatisfactory with a 6-year event free survival (EFS) of only 24%.

Based on existing data, bortezomib-containing regimens are currently accepted at many centers as an induction treatment option for patients with symptomatic MM, particularly if it is planned to offer subsequent high-dose therapy with ASCT. So we will use bortezomib-containing regimens as induction prior to this novel conditioning regimen. The objective of the present study is to compare the toxicity and therapeutic efficacy of a new high-dose regimen using dose-escalation of BOR, BU and MEL for ASCT in the Korean patients with MM. The patients should be treated with bortezomib-containing regimens as an induction therapy before ASCT. We will specifically analyze (i) the efficacy of the conditioning regimen in improving the pre-ASCT status, response rate (ii) engraftment and transplant-related mortality (TRM) and (iii) the impact on survival including progression-free survival (PFS) and overall survival (OS).

Triple combination of conditioning will enhance the response rate after ASCT, and will improve not only PFS, but also OS. We think that data from this study may further strengthen feasibility of BOR in conditioning prior to ASCT.


Condition Intervention Phase
Multiple Myeloma Patients Who Candidate for Autologous Peripheral Blood Stem Cell Transplantation
Drug: Bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-label, Prospective, Multicenter Study to Evaluate the Efficacy and Safety of the Lower Dose of Bortezomib Plus Busulfan and Melphalan as a Conditioning Regimen in Patients With Multiple Myeloma Undergoing Autologous Peripheral Blood Stem Cell Transplantation- KMM103 Study

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • Maximally tolerated dose (Phase 1) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • CR and near CR (Phase 2) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 53
Study Start Date: October 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Busulfan Drug: Bortezomib
Bortezomib i.v. 0.7, 1.0 and 1.3 mg/m²/day
Other Name: VELCADE®
Active Comparator: Melphalan Drug: Bortezomib
Bortezomib i.v. 0.7, 1.0 and 1.3 mg/m²/day
Other Name: VELCADE®

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a confirmed diagnosis of multiple myeloma (MM)
  • Symptomatic MM (multiple myeloma with related organ or tissue damage)
  • The MM patients with induction chemotherapy with bortezomib-containing regimens (bortezomib±steroid±adrimycin)
  • The MM patients who performed the peripheral blood stem cell collection and appropriate stem cell counts (CD34+ cells 2 x 106/kg).
  • Age 20-65 years
  • Performance status: ECOG (Eastern Cooperative Oncology Group) 0-2.
  • Patient has measurable disease, defined as follows: measurable disease is defined as serum M-protein ≥ 1 g/dL or urine M-protein ≥ 200 mg/24 hours when the patients started the primary induction therapy.
  • Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormalities
  • Adequate liver functions: - Transaminase (AST/ALT) < 3 X upper normal value - Bilirubin < 2 X upper normal value
  • Adequate hematological function: Platelet count ≥ 75 x 109/L, hemoglobin ≥ 8 g/dL, (Prior RBC transfusion or recombinant human erythropoietin use is allowed), absolute neutrophil count (ANC) ≥ 1.0 x 109/L
  • A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause.
  • Expected survival 6 months
  • Informed consent

Exclusion Criteria:

  • Systemic AL amyloidosis, smoldering multiple myeloma or MGUS.
  • Patient with plasma cell leukemia (> 20% plasma cells in the PB and an absolute plasma cell count of at least 2000/μL)
  • Patients who received an extensive radiation therapy within 4 weeks
  • Patient is known to be Human Immunodeficiency Virus (HIV) positive.
  • Patient has known clinically active Hepatitis B or C.
  • Previous renal transplantation
  • Severe peripheral neuropathy (Grade 2 or higher as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0)
  • Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri
  • Pregnant or lactating women, women of childbearing potential not employing adequate contraception
  • Other serious illness or medical conditions i. Uncontrolled or severe cardiovascular disease, including myocardial infarction, within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis ii. History of significant neurological or psychiatric disorders including dementia or seizures iii. Active uncontrolled infection (viral, bacterial or fungal infection) iv. Active ulcers detected at gastroscopy v. Other serious medical illnesses
  • Known hypersensitivity to any of the study drugs or its ingredients (i.e., hypersensitivity to compounds containing boron or mannitol)
  • Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01255527

Locations
Korea, Republic of
National Cancer Center Recruiting
Goyang, Korea, Republic of
Contact: Hyeon-Seok Eom, MD, Ph.D    82-31-1588-8110      
Gachon University Gill Hospital Recruiting
Incheon, Korea, Republic of
Contact: Jae-Hoon Lee, MD, Ph.D    82-32-1577-2299      
ASAN Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Chul-Won Suh, MD, Ph.D    82-2-1688-7575      
Ewha Womans University Mokdong Hospital Recruiting
Seoul, Korea, Republic of
Contact: Yeong-Chul Mun, MD, Ph.D    82-2-2650-5114      
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Ki-Hyun Kim, MD, Ph.D    82-2-1599-3114      
Contact: Seok-Jin Kim, MD, Ph.D    82-2-1599-3114      
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Sung-Soo Yoon, MD, Ph.D    82-2-2072-2114      
Seoul St. Mary's Hospital Recruiting
Seoul, Korea, Republic of
Contact: Chang-Ki Min, MD, Ph.D    82-2-2258-6053      
Severance Hospital Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Jin-Seok Kim, MD, Ph.D    82-2-2228-1972      
Sponsors and Collaborators
Yonsei University
  More Information

No publications provided

Responsible Party: Yonsei University
ClinicalTrials.gov Identifier: NCT01255527     History of Changes
Other Study ID Numbers: 4-2010-0482
Study First Received: December 6, 2010
Last Updated: June 1, 2013
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Busulfan
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014